Hematopoietic progenitor cells from patients with myelodysplastic syndromes: in vitro colony growth and long-term proliferation.

It is known that the levels of hematopoietic progenitor cells (HPC) are greatly reduced in the majority of patients with myelodysplastic syndromes (MDS). To date, however, only limited information exists on the growth kinetics of these cells in long-term marrow cultures (LTMC), particularly in terms of erythroid and multipotent progenitors. In the present study, we have determined the HPC content in the bone marrow of 12 MDS patients and followed the proliferation kinetics of myeloid (including granulocyte, macrophage and granulocyte macrophage), erythroid (including early and late) and multipotent progenitor cells in LTMC throughout a 7-week culture period. Both the non-adherent and adherent fractions of the cultures were analyzed, so we were able to look at progenitor cells in suspension and those that physically associated to the stromal cell layer developed in culture. All 12 patients were grouped based on their FAB subtype and the in vitro growth of the HPC was analyzed accordingly. The results presented here indicate that in the majority of MDS patients, pronounced deficiencies exist both in the content and the long-term proliferation of marrow HPC. Such deficiencies were particularly evident for multipotent progenitors and those committed to the erythroid lineage, in which alterations in the maturation process also seem to be present. Our results suggest that, at least in some patients, HPC--besides showing an impaired proliferative capacity--lose their ability to adhere to the stromal cell layers developed in culture. RA patients showed the less affected in vitro HPC growth, whereas HPC from RAEB and RAEB-t showed a markedly deficient growth in culture. Interestingly, myelopoiesis was significantly increased in cultures of CMML patients. These results give some new insights into the biology of MDS-derived HPC.

Cytogenetic findings in 303 Mexican patients with de novo acute myeloblastic leukemia.

In this report we show the chromosomal changes seen in a group of 303 Mexican patients with de novo Acute Myeloblastic Leukemia (AML). Two hundred forty-two patients were diagnosed and treated at two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS). These are the Centro Medico Nacional Siglo XXI and Centro Medico La Raza Hospitals; the remaining 61 patients were diagnosed and treated at the Hospital General de Mexico (HGM). Clonal abnormalities were detected in 75.6% of the patients; this result agrees with what has been reported in other large series of AML studies. The incidence of changes per hospital was similar in patients from the IMSS hospitals (72-75%), while an increase was seen in patients from the HGM (85.2%). The chromosomal changes seen in this study in order of frequency were: t(15;17)[18.8%], t(9;22)[9.2%], miscellaneous chromosomal changes (mainly rearrangements of chromosomes 1,2,3,12y17)[8.2%], abnormalities of 16q22 [7.3%], t(8;21)[6.3%], -7/del(7q)[5.6%], t(6;9)[5.3%], and abnormalities of 11q23 [4.6%]. We reported an increase in the incidence of certain types of chromosomal changes seen in cases of AML, in comparison with reports from other countries. These differences could be due to methodological variations, although ethnic, socioeconomic and nutritional differences must not be disregarded. We support this finding when comparing distribution of changes in the population of patients seen in the IMSS hospitals with those from the HGM; the main difference lies in the socioeconomic level.

Treatment results of 23 cases of severe aplastic anemia with lymphocytapheresis.

We report the results of 23 patients with aplastic anemia (AA) treated with a program of 14 lymphocytapheresis (LC). Treatments were performed with apheresis machines, models Haemonetics 30-S and Baxter CS3000, using the standard program. This procedure was done because AA in many cases appears as a result of the action of a T cell population that inhibits hematopoiesis. Theoretically, removal of this clonal population would produce hematopoietic recovery. Of the total of 23 patients, 9 were excluded for final evaluation of treatment results because 7 died during or shortly after treatment (0.7-3 months); one patient abandoned treatment after three LC and another died 7 months later because of transformation to acute leukemia. The remaining 14 patients were included in the final evaluation of treatment; seven females and seven males, average age 46.1 years (range 22-69); 13 with severe, and one with moderate AA; 11 with recently diagnosed, and 3 with chronic AA; 12 without previous treatment and two treated before with antilymphocyte globulin + oxymetholone (OXM) + cyclosporine A (CsA) with transient partial remission (PR). Besides lymphocytapheresis, 13 patients received OXM; 4 of them GM-CSF and one low dose CsA. Four patients had complete remission lasting > 59.5 months (range 42-78); eight PR (average duration of > 38.6 months), and two minimal remission (> 37 and 29 months). Platelet, reticulocyte and granulocyte counts increased on average at 48.7, 73.3 and 91.4 days, respectively. In conclusion, 14 (60.8%) of 23 patients with AA showed an improvement related to LC treatment, with a survival probability of 63% from the fourth month, the latter with an added beneficial effect of the other therapies used. Larger numbers of patients have to be treated with LC to determine its real usefulness, mechanism of action and the best conditions for its use.

[Blood erythropoietin levels in healthy subjects studied in the valley of Mexico]. / Niveles séricos de eritropoyetina en sujetos sanos estudiados en el valle de México.

Erythropoietin (EPO) is the hematopoietic growth factor that regulates red cell production. There is a direct relationship between its secretion and tissue hypoxia. Above sea level, oxygen concentration diminishes. This causes an increase of hemoglobin and hematocrit; this effect could be the consequence of higher EPO levels. Currently, evaluation of baseline serum EPO levels is very important in the differential diagnosis of anemia and erythrocytosis. The purpose of the present work was to report the EPO levels on a group of healthy blood donors living in Mexico City, 2,240 m above sea level. Two-hundred twenty blood donors were selected to measure serum EPO; there were 168 males and 52 females. Median EPO levels of the entire population were 7.5 mU/mL (percentile interval, PI, 1-18). Median EPO levels were 7.6 (PI 1-18) and 7.5 (PI 1-16.9) for men and women, respectively. We did not find differences in serum EPO levels among previous reports in other populations and the values determined in this study.